Trospium has been shown to reduce bladder hyperactivity in patients suffering from urinary incontinence and exerts spasmolytic effects on the bladder by inhibiting the effects of acetylcholine on smooth muscle. Trospium has selectivity for muscarinic receptors over nicotinic receptors and as a result, no blocking effects are observed at skeletal neuromuscular junctions. Active metabolites of trospium exert antimuscarinic activities that may account for part of the therapeutic activity of trospium.
In particular, compounds within the class of antimuscarinic drugs for urinary incontinence, including terodiline, tolterodine and oxybutynin, cause severe cardiac electrophysiological side effects. These adverse side effects are associated with prolonged QT interval and include but are not limited to ventricular fibrillation and cardiac arrhythmias, such as torsades de pointes. This is the same type of potentially lethal cardiac side effects that led to the withdrawal of several medications from the market; examples of drugs that have been withdrawn of that reason are the antihistamine drug terfenadine, the antihistamine drug astemizole, the prokinetic drug cisapride and the incontinence drug terodiline that is mentioned above.
No known reference teaches or enables the methods of the present invention comprising administering trospium to a human while avoiding said adverse cardiac side effects; nor do the published references alone or in combination suggest these methods.